CHANGES IN EXTRACELLULAR NITRITE AND NITRATE LEVELS AFTER INHIBITION OF GLIAL METABOLISM WITH FLUOROCITRATE

The role of glial cells in nitric oxide production in the cerebellum o f conscious rats was investigated with a glial selective metabolic inh ibitor, fluorocitrate. The levels of nitric oxide metabolites (nitrite plus nitrate) in the dialysate following in vivo microdialysis progre ssively increased to more than 2-fold the basal levels during a 2-h in fusion of fluorocitrate (1 mM), and the increase persisted for more th an 2 h after the treatment. Pretreatment with N-G-nitro-L-arginine met hyl ester attenuated the fluorocitrate-induced increase in nitric oxid e metabolite levels. None of the glutamate receptor antagonists, inclu ding D(-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2, 3-dione, and (+/-)-alpha-methyl-4-carboxyphenylglycine, inhibited the fluorocitrate-induced increase. The L-arginine-induced increase was si gnificantly reduced by fluorocitrate treatment, while N-methyl-D-aspar tate, lpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and ns- (+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid increased nitric oxide metabolites levels in the fluorocitrate-treated rats, as much as in control animals. These results suggest that glial cells play an im portant role in modulating nitric oxide production in the cerebellum b y regulating L-arginine availability.